scholarly journals Factors Predicting Treatment of World Trade Center-Related Lung Injury: A Longitudinal Cohort Study

2020 ◽  
Vol 17 (23) ◽  
pp. 9056
Author(s):  
Barbara Putman ◽  
Lies Lahousse ◽  
David G. Goldfarb ◽  
Rachel Zeig-Owens ◽  
Theresa Schwartz ◽  
...  
Keyword(s):  
Lung Injury ◽  
World Trade ◽  
Proportional Hazards ◽  
World Trade Center ◽  
Patient Characteristics ◽  
Forced Expiratory Volume ◽  
Cox Proportional Hazards ◽  
Beta Agonist ◽  
Cox Proportional Hazards Models ◽  
Trade Center

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001–10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001–1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV1), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001–10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005–10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV1, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.

scholarly journals Metabolomics of World Trade Center-Lung Injury: a machine learning approach

2018 ◽  
Vol 5 (1) ◽  
pp. e000274 ◽  
Author(s):  
George Crowley ◽  
Sophia Kwon ◽  
Syed Hissam Haider ◽  
Erin J Caraher ◽  
Rachel Lam ◽  
...  
Keyword(s):  
Machine Learning ◽  
Lung Function ◽  
Lung Injury ◽  
World Trade ◽  
World Trade Center ◽  
Forced Expiratory Volume ◽  
Machine Learning Techniques ◽  
Maximal Class ◽  
Class Separation ◽  
Trade Center

IntroductionBiomarkers of metabolic syndrome expressed soon after World Trade Center (WTC) exposure predict development of WTC Lung Injury (WTC-LI). The metabolome remains an untapped resource with potential to comprehensively characterise many aspects of WTC-LI. This case–control study identified a clinically relevant, robust subset of metabolic contributors of WTC-LI through comprehensive high-dimensional metabolic profiling and integration of machine learning techniques.MethodsNever-smoking, male, WTC-exposed firefighters with normal pre-9/11 lung function were segregated by post-9/11 lung function. Cases of WTC-LI (forced expiratory volume in 1s <lower limit of normal, n=15) and controls (n=15) were identified from previous cohorts. The metabolome of serum drawn within 6 months of 9/11 was quantified. Machine learning was used for dimension reduction to identify metabolites associated with WTC-LI.Results580 metabolites qualified for random forests (RF) analysis to identify a refined metabolite profile that yielded maximal class separation. RF of the refined profile correctly classified subjects with a 93.3% estimated success rate. 5 clusters of metabolites emerged within the refined profile. Prominent subpathways include known mediators of lung disease such as sphingolipids (elevated in cases of WTC-LI), and branched-chain amino acids (reduced in cases of WTC-LI). Principal component analysis of the refined profile explained 68.3% of variance in five components, demonstrating class separation.ConclusionAnalysis of the metabolome of WTC-exposed 9/11 rescue workers has identified biologically plausible pathways associated with loss of lung function. Since metabolites are proximal markers of disease processes, metabolites could capture the complexity of past exposures and better inform treatment. These pathways warrant further mechanistic research.

scholarly journals A contemporary survival analysis of individuals with cystic fibrosis: a cohort study

2014 ◽  
Vol 45 (3) ◽  
pp. 670-679 ◽  
Author(s):  
Anne L. Stephenson ◽  
Melissa Tom ◽  
Yves Berthiaume ◽  
Lianne G. Singer ◽  
Shawn D. Aaron ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Proportional Hazards ◽  
Patient Characteristics ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Cox Proportional Hazards Models ◽  
Increased Risk

Previously established predictors of survival may no longer apply in the current era of cystic fibrosis (CF) care. Our objective was to identify risk factors associated with survival in a contemporary CF population.We used the Canadian CF Registry, a population-based cohort, to calculate median age of survival and summarise patient characteristics from 1990 to 2012. Clinical, demographic and geographical factors, and survival were estimated for a contemporary cohort (2000–2012) using Cox proportional hazards models.There were 5787 individuals in the registry between 1990 and 2012. Median survival age increased from 31.9 years (95% CI 28.3–35.2 years) in 1990 to 49.7 years (95% CI 46.1–52.2 years) in the most current 5-year window ending in 2012. Median forced expiratory volume in 1 s improved (p=0.04) and fewer subjects were malnourished (p<0.001) over time. Malnourished patients (hazard ratio (HR) 2.1, 95% CI 1.6–2.8), those with multiple exacerbations (HR 4.5, 95% CI 3.2–6.4) and women with CF-related diabetes (HR 1.8, 95% CI 1.2–2.7) were at increased risk of death.Life expectancy in Canadians with CF is increasing. Modifiable risk factors such as malnutrition and pulmonary exacerbations are associated with an increased risk of death. The sex gap in CF survival may be explained by an increased hazard for death in women with CF-related diabetes.

scholarly journals Risk factors for incident prostate cancer in a cohort of world trade center responders

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sean A. P. Clouston ◽  
Peifen Kuan ◽  
Roman Kotov ◽  
Soumyadeep Mukherjee ◽  
Patricia Thompson-Carino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Incidence ◽  
World Trade ◽  
Proportional Hazards ◽  
Traumatic Event ◽  
World Trade Center ◽  
Cox Proportional Hazards ◽  
Stressful Events ◽  
Prostate Cancer Incidence ◽  
Trade Center

Abstract Background Despite a relatively young average age and no routine screening, prostate cancer is one of the most common cancers in men who worked at the World Trade Center (WTC) following the 9/11/2001 disaster. This study evaluated whether re-experiencing stressful memories of a traumatic event was associated with prostate cancer incidence. Methods Participants were males from one clinical center that monitors the health of first-responders (N = 6857). Monitoring began in July 2002 and occurs annually but does not include prostate cancer screening. Severity of physical exposures and of re-experiencing memories and stress responses were measured at study enrollment using standardized and validated methods in all participants. The outcome was incidence of diagnosed prostate cancer after enrollment (n = 68). Bivariate analyses provided age-adjusted incidence rates (aIR). Cox proportional hazards modeling was used to calculate incidence; hazards ratios (HR) were reported. Results The mean age of responders on 9/11/2001 was 37.9 years. Prostate cancer incidence was lowest in responders with no re-experiencing stress (aIR = 250.83/100,000 person-years, [233.41–268.25]) and highest in responders with severe re-experiencing stress (aIR = 818.49/100,000 person-years, [801.07–835.91]). Cox proportional hazards regression revealed that re-experiencing the stressful events of 9/11/2001 was associated with increased prostate cancer incidence (HR = 1.96 [1.26–3.05], P = 0.003), even upon adjusting for confounders. Conclusions This is the first study to identify a positive association between re-experiencing a traumatic event and prostate cancer incidence. Our results are consistent with recent rodent model evidence demonstrating a direct biological link between stress pathways and prostate tumorigenesis and offer new hypotheses in the causality of prostate cancer.

scholarly journals Cardiovascular biomarkers predict susceptibility to lung injury in World Trade Center dust-exposed firefighters

2012 ◽  
Vol 41 (5) ◽  
pp. 1023-1030 ◽  
Author(s):  
Michael D. Weiden ◽  
Bushra Naveed ◽  
Sophia Kwon ◽  
Soo Jung Cho ◽  
Ashley L. Comfort ◽  
...  
Keyword(s):  
Lung Injury ◽  
World Trade ◽  
World Trade Center ◽  
Trade Center ◽  
Cardiovascular Biomarkers

Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
Bradley Alexander McGregor ◽  
Daniel M. Geynisman ◽  
Mauricio Burotto ◽  
Camillo Porta ◽  
Cristina Suarez Rodriguez ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Objective Response ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Wald Test ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Published Data ◽  
Cox Proportional Hazards Models

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trialof P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]

scholarly journals Survival of patients treated with extended-hours haemodialysis in Europe: an analysis of the ERA-EDTA Registry

2019 ◽  
Vol 35 (3) ◽  
pp. 488-495 ◽  
Author(s):  
Thijs T Jansz ◽  
Marlies Noordzij ◽  
Anneke Kramer ◽  
Eric Laruelle ◽  
Cécile Couchoud ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Treatment Practices ◽  
Improve Patient Survival ◽  
Cox Proportional Hazards Models ◽  
Crude Mortality ◽  
The Usa ◽  
Secondary Analyses ◽  
Improve Patient

Abstract Background Previous US studies have indicated that haemodialysis with ≥6-h sessions [extended-hours haemodialysis (EHD)] may improve patient survival. However, patient characteristics and treatment practices vary between the USA and Europe. We therefore investigated the effect of EHD three times weekly on survival compared with conventional haemodialysis (CHD) among European patients. Methods We included patients who were treated with haemodialysis between 2010 and 2017 from eight countries providing data to the European Renal Association–European Dialysis and Transplant Association Registry. Haemodialysis session duration and frequency were recorded once every year or at every change of haemodialysis prescription and were categorized into three groups: CHD (three times weekly, 3.5–4 h/treatment), EHD (three times weekly, ≥6 h/treatment) or other. In the primary analyses we attributed death to the treatment at the time of death and in secondary analyses to EHD if ever initiated. We compared mortality risk for EHD to CHD with causal inference from marginal structural models, using Cox proportional hazards models weighted for the inverse probability of treatment and censoring and adjusted for potential confounders. Results From a total of 142 460 patients, 1338 patients were ever treated with EHD (three times, 7.1 ± 0.8 h/week) and 89 819 patients were treated exclusively with CHD (three times, 3.9 ± 0.2 h/week). Crude mortality rates were 6.0 and 13.5/100 person-years. In the primary analyses, patients treated with EHD had an adjusted hazard ratio (HR) of 0.73 [95% confidence interval (CI) 0.62–0.85] compared with patients treated with CHD. When we attributed all deaths to EHD after initiation, the HR for EHD was comparable to the primary analyses [HR 0.80 (95% CI 0.71–0.90)]. Conclusions EHD is associated with better survival in European patients treated with haemodialysis three times weekly.

scholarly journals Vitamin D Status in Patients With Stage IV Colorectal Cancer: Findings From Intergroup Trial N9741

2011 ◽  
Vol 29 (12) ◽  
pp. 1599-1606 ◽  
Author(s):  
Kimmie Ng ◽  
Daniel J. Sargent ◽  
Richard M. Goldberg ◽  
Jeffrey A. Meyerhardt ◽  
Erin M. Green ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Statistical Power ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Stage Iv Colorectal Cancer ◽  
Cox Proportional Hazards Models

Purpose Previous studies have suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. Patients and Methods We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Results Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Conclusion Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients.

Differences in survival for metastatic colorectal cancer patients by lines of therapy received.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14016-e14016
Author(s):  
Brian S. Seal ◽  
Benjamin Chastek ◽  
Mahesh Kulakodlu ◽  
Satish Valluri
Keyword(s):  
Proportional Hazards ◽  
Survival Rates ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Research Database ◽  
First Line ◽  
Cox Proportional Hazards Models ◽  
Stage 4 ◽  
Similar Survival ◽  
The Impact

e14016 Background: Improvements in survival for advanced-stage CRC patients who receive chemotherapy have been reported. We compared survival rates for patients with 3+ vs. <3 lines of therapy. Methods: Adult patients with a diagnosis of CRC between 01/01/05 and 05/31/10 were identified from the Impact Intelligence Oncology Management (IIOM) registry. Patients with either stage 4 CRC at original diagnosis or development of metastasis were included. Registry data included original stage and date of diagnosis. Linked healthcare claims from the Life Sciences Research Database, a large US health insurance database affiliated with OptumInsight, were used to identify lines of therapy after metastases and patient characteristics. Death data were obtained from the Social Security Administration’s master death file. Patients were categorized by number of lines of therapy received (0, 1, 2, 3+) and original stage at diagnosis (0-2, 3, 4, unknown). Survival following metastases was evaluated using Cox proportional hazards models controlling for lines of therapy received, stage, and other patient characteristics. Results: 598 patients, followed for a mean of 653 days after becoming metastatic, were included. Mean unadjusted length of follow-up was lowest among patients who received no chemotherapy (516 days) or only 1 line (511 days), and increased to 627 days for those with 2 lines and 930 days for those with 3+ lines. However, multivariate analysis indicated that patients with 3+ lines had comparable survival vs. those with 0 (HR=0.79), 1 (HR=1.59), or 2 (HR=1.15) lines of therapy (p>0.05 for all comparisons). Compared to patients who presented with stage 4 CRC, those who progressed from stage 0-2 (HR=1.22), stage 3 (HR=0.83), or unknown stage (HR=1.18) had similar survival after metastases (p>0.05 for all comparisons). After excluding 94 patients who didn’t receive chemotherapy, patients treated with an oxaliplatin-based regimen (HR=1.28; p=0.24) in first line had similar survival compared to patients treated with an irinotecan-based or anti-EGFR regimen in first line. Conclusions: Lines of therapy received and initial stage were not associated with survival after development of metastases.

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